Lethality associated with Bacillus anthracis (B. anthracis) infection during the 2001 outbreak was characterized by shock unresponsive to conventional hemodynamic support. While lethal toxin (LeTx) production is central to the pathogenesis of such shock, the mechanisms underlying these cardiovascular effects are poorly understood and require elucidation to improve outcome from this highly lethal infection. Intact brainstem and hypothalamic function, and the associated hypothalamic-pituitary-adrenal axis (HPA axis), contribute to coordinated cardiovascular responses during states of hemodynamic instability (low blood pressure) such as sepsis. While considerable research has characterized the potential pathophysiologic effects of more common bacterial toxins such as lipopolysaccharide (LPS) on these structures, this has not been done with LeTx. Findings from our laboratory suggest however that different from shock with LPS, which appears to stimulate brain stem and hypothalamic function, shock with LeTx may suppress of this function. During the development of early shock with LeTx in both rats and canines, heart rate does not increase as would be expected. Furthermore in rats, this hypotension is not associated with the increases in plasma catecholamines that occurs with similar levels of shock with LPS challenge. The goal of the present investigation is to characterize the effects of LeTx on brainstem and hypothalamic activity and compare them to those of LPS using brain magnetic resonance imaging (MRI), central nervous system histopathology, measures of circulating catecholamines, cortisol and adrenocorticotropic hormone levels, and cardiovascular measures in rats. The MRI scanning will include both manganese enhanced scanning (MEMRI) to assess brain stem and hypothalamic neuronal activity and gadolinium enhanced scanning to assess blood brain barrier (BBB) integrity. We hypothesize that compared to LPS, shock with similarly lethal LeTx challenge will be associated with evidence of suppressed brainstem and hypothalamic autonomic and HPA axis activity. The study will include 2 parts. The first part is a pilot study designed to determine optimal timing for the MEMRI scanning procedure. The second part will include three cohorts of animals; one undergoing MEMRI, one undergoing gadolinium enhanced MRI and one undergoing measures of circulating catecholamines, cortisol and ACTH. All animals will have serial hemodynamic measures performed and brain tissue removed for histological studies.